Lecture 10 - Antigen Processing and Presentation

Question 1

Which part of MHC is polymorphic?

Answer 1

The binding pocket

Question 2

Which parts of a peptide interact with TCR?

Answer 2

Non-anchor residues

Question 3

How do peptides bind into MHC?

Answer 3

Using anchor side chains

Question 4

Must all pockets be perfectly filled for peptide to bind MHC?

Answer 4

No

Question 5

What does alpha3 bind?

Answer 5

CD8

Question 6

What does Beta2 of MHCII bind?

Answer 6

CD4

Question 7

Difference in shape between MHCI and II

Answer 7

MHCI is more closed. Peptide termini aren’t exposed

MHCII is more open. Peptide termini are exposed

Question 8

Why are peptide termini bound to MHCI not exposed?

Answer 8

N- and C-termini need to form conserved hydrogen bonds in order to bind,

This also restricts peptide length

Question 9

Which MHC can bind multiple peptides with the same epitope?

Answer 9

MHCII

Peptides with the same core sequence

Question 10

How can MHCII bind multiple peptides with the same epitope?

Answer 10

Peptides have same core sequence, but have been differently processed. Therefore have different sequences either side of core sequence.

MHCII can have exposed peptide termini

Question 11

What are anchor residues?

Answer 11

Residues that bind pockets

Question 12

Limit on MHCII structure

Answer 12

Need to have conserved structures to bind invariant chain

Question 13

Who is polygeny good for?

Answer 13

Individual

Question 14

Who is polymorphism good for?

Answer 14

Population

Question 15

What is antigen processing?

Answer 15

Intracellular proteolytic generation of MHC-binding peptides

Question 16

Can MHC bind self peptides?

Answer 16

Yes. Very frequently.

Question 17

MHCII processing pathway
1)
2)
3)
4)

Answer 17

1) Internalisation of protein
2) Protein degraded to small peptides in late endosome by acid.
3) MHCII bound to invariant chain leaves ER, binds to endosome. Forms MIIC compartment
4) MHCII/antigen complex, expressed on surface

Question 18

Which proteins are expressed on MHCII?

Answer 18

Proteins in endosomal/lysosomal network. Many self antigens

Question 19

Why do hapens need a carrier?

Answer 19

Too small to be able to fit into MHC without carrier

Can’e elicit a T cell response

Question 20

Why does MHCII have invariant chain?

Answer 20

So that MHCII doesn’t bind peptides in the ER.

Very large number of self antigens in ER, don’t want these expressed on MHC

Question 21

Roles of invariant chain

Answer 21

1) Prevent binding of unwanted proteins to MHCII

2) Target MHCII to endosomal network

Question 22

What is HLA-DM?

Answer 22

Removes CLIP from MHCII in MIIC

Question 23

What removes CLIP from MHCII?

Answer 23

HLA-DM

Question 24

Where does CLIP come from?

Answer 24

Degradation of invariant chain

Some is left in the MHC binding groove

Question 25

Where is invariant chain degraded?

Answer 25

MIIC

Question 26

Very important proteins in MHCI pathway
1)
2)

Answer 26

1) Proteosome

2) Transporter associated with Antigen Processing (TAP)

Question 27

Where do MHCI stay until binding peptide?

Answer 27

ER

Question 28

Which MHC does invariant chain bind?

Answer 28

MHCII